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. Author manuscript; available in PMC: 2011 Jul 1.

Published in final edited form as: Cancer J. 2010 Jul–Aug;16(4):382–391. doi: 10.1097/PPO.0b013e3181eaca65

A. DC are most efficient at acquiring antigen when they are in their immature state through mechanisms that include phangocytosis, endocytosis and receptor mediated uptake. After encountering TLR ligands, they undergo maturation and upregulate HLA molecules (which present peptide antigens to T cell receptors on T cells) as well as co-stimulatory molecules such as CD80 and CD86, which interact with CD28 on T cells. DC also produce cytokines (IL-12, type I IFN) that aid in priming of CD4+ helper cells and cytolytic T cells. B. DC utilize endogenous and exogenous pathways to process and present antigens to CD8+ T cells. In the endogenous pathway, exemplified by virus infection or transduction of cells with RNA or DNA encoding antigens, antigen is processed in the cytoplasm by the proteosome and then transported into the ER where further processing can take place and peptides access newly synthesized HLA class I molecules. The peptide-HLA complex is then transported to the cell surface where it can interact with the T cell receptor. In the exogenous pathway, dying virus- infected cells or tumor cells (e.g. following chemotherapy or irradiation) are phagocytosed by DC and crosspresented to T cells. Dying tumor cells also release factors that activate DC via TLRs or components of the inflammasome. Antigens from these cells may access the cytoplasm and intersect with the conventional endogenous pathway of antigen processing. Alternatively, they may be processed within the endosomes themselves and acquired by recycling class I molecules which return to the cell surface. The exogenous pathway explains how antigens from dead cells can be acquired and presented to T cells.

A. DC are most efficient at acquiring antigen when they are in their immature state through mechanisms that include phangocytosis, endocytosis and receptor mediated uptake. After encountering TLR ligands, they undergo maturation and upregulate HLA molecules (which present peptide antigens to T cell receptors on T cells) as well as co-stimulatory molecules such as CD80 and CD86, which interact with CD28 on T cells. DC also produce cytokines (IL-12, type I IFN) that aid in priming of CD4+ helper cells and cytolytic T cells. B. DC utilize endogenous and exogenous pathways to process and present antigens to CD8+ T cells. In the endogenous pathway, exemplified by virus infection or transduction of cells with RNA or DNA encoding antigens, antigen is processed in the cytoplasm by the proteosome and then transported into the ER where further processing can take place and peptides access newly synthesized HLA class I molecules. The peptide-HLA complex is then transported to the cell surface where it can interact with the T cell receptor. In the exogenous pathway, dying virus- infected cells or tumor cells (e.g. following chemotherapy or irradiation) are phagocytosed by DC and crosspresented to T cells. Dying tumor cells also release factors that activate DC via TLRs or components of the inflammasome. Antigens from these cells may access the cytoplasm and intersect with the conventional endogenous pathway of antigen processing. Alternatively, they may be processed within the endosomes themselves and acquired by recycling class I molecules which return to the cell surface. The exogenous pathway explains how antigens from dead cells can be acquired and presented to T cells.